Medical Device Quality

Management System
Albert T.W. Li
Industrial Technology Research Institute

AHWP TC Training Workshop, Taipei

November 3, 2012
1
Copyright 2012 ITRI

Content
GHTF Medical Device Regulatory Model
QMS for SMEs
Revision of ISO 13485

Copyright 2012 ITRI

Medical Device Regulation Model

Ref. GHTF/AHWG-GRM/N1R13:2011 Global Harmonization Task Force with modifications
Product Lifecycle Start

Definitions

Device Requirements
/Intended Use

The Essential Principles/

Standards

Design Input/Specifications

QMS Design Control/Risk

Analysis

Design

QMS Design Control/ Risk

Assessment

Design Verification

QMS

Labelling

Pilot Production

QMS Design Validation/Risk

Assessment/ Process
Validation

Design Validation

Clinical Evidence

Manufacturing

QMS

QMS Service

Device Classification

Conformity Assessment Approval

Registration/ Licencing

Placing on the Market

Market Performance

Post Market Surveillance

and Vigilance

Obsolescence
Adverse Event Reporting
Product Lifecycle End

Copyright 2012 ITRI

Content
GHTF Medical Device Regulatory Model
QMS for SMEs
Revision of ISO 13485

Copyright 2012 ITRI

Medical Device Innovation Engine: SMEs

Economic growth in the medical device industry is fueled by new

product development. Furthermore, a significant proportion of that new
product development comes from small and emerging
companies.(Centers for Medicare & Medicaid Services, HHS, U.S.,
Market Update Reports, 2003)

Taiwan: 1,034 Class I MD manufacturers, 506 Class II/II MD

manufacturers , 30,000 employees

U.S: 5,300 MD manufacturers, 365,000 employees, 15% manufacturers

with more than 100 employees, 73% manufacturers with employees less
than 20

EU: 8,750 MD Manufacturers, 534,000 employees, 80% manufacturers

are SMEs (1,187 manufacturers with 50~250 employees, 1,940
manufacturers with 10~50 employees, 3,702 manufacturers with
employees less than 10

UK: 3,000 MD manufacturers , 98% manufacturers with employees less

than 100, 65% manufacturers with employees less than 10.

Copyright 2012 ITRI

QMS and Medical Device

Safety and Effectiveness
The (GMP/QS) regulation requires
that various specifications and controls be established for
devices;
that devices be designed under a quality system to meet
these specifications;
that devices be manufactured under a quality system; that
finished devices meet these specifications;
that devices be correctly installed, checked and serviced;
that quality data be analyzed to identify and correct quality
problems; and
that complaints be processed.

Thus, the QS regulation helps assure that medical

devices are safe and effective for their intended use.
US FDA Medical Device Quality Systems Manual
6
Copyright 2012 ITRI

Medical Device QMS Standards

1978 US FDA 21 CFR 820 Medical Device Good
Manufacturing Practice
ISO 9001: 1987
ISO 9001: 1994, ISO 9002: 1994, ISO 9003: 1994, ISO 9004:
1994
ISO 13485: 1996, ISO 13488: 1996 (based on ISO 9001: 1994,
ISO 9002: 1994)
1996 US FDA Quality System Regulation/GMP
ISO 9001: 2000
ISO 13485: 2003 (stand alone standard)
ISO 9001: 2008

7
Copyright 2012 ITRI

Regulatory Auditing
Certification

Accreditation
Organizations
ISO/IEC 17011
QMS Certification Bodies
(ISO/IEC 17021)
MD Manufacturers
ISO 13485: 2003
(ISO 9001: 2000
ISO 1400)

Regulatory Auditing (examples)

Canada
Medical
Device
Regulation

European
Union
AIMD/MDD
/IVDD

US
21 CFR 820
MDUFMA

Taiwan
PAA, GMP

Health Canada

EU
Competent
Authorities

US FDA CDRH
TPRB

TFDA

Notified Bodies

FDA QSR
Accredited
Persons

GMP
Authorized
Auditing
Organizations

CMDCAS
Registrars

Higher Risk MD Manufacturers

CMDCAS, GMP, EN ISO 13485: 2003

8
Copyright 2012 ITRI

ISO 13485:2003
4. QMS

5.Management Responsibility

4.1
4.2
General
Documentation
requirements

5.1
Management
Commitment

5.2
Customer
Focus

5.3
Quality
Policy

5.4
Planning

5.5
5.6
Responsibility
Management
Authority,
responsibility
Communication

7.Product Realization
7.1
Planning of
product
realization

7.2
Customer-related
processes

6.Resource Management
6.1
6.2
6.4
Provision
6.3
Human
Work
of
infrastructure
resources
environment
resources

Copyright 2012 ITRI

7.3
Design
And
development

7.4
Purchasing

7.5
Production
and service
provision

7/8Measurement, analysis and improvement

7.6
8.3
8.2
Control
control of
8.1
Monitoring
Of monitoring
NonGeneral
and
and measuring
conforming
measurement
devices
product

8.4
8.5
Analysis
improvement
of data

ISO 13485 Subsystems

Product Related Subsystems
Design and
Development

Management

Product
Documentation

CAPA

Purchasing
Control

Production and
Manufacturing

Document
and Record

Customer
Related

Supporting Subsystems

GHTF/SG4/N30R21:2010 Part 2: Regulatory Auditing Strategy

Copyright 2012 ITRI

10

Further Readings:
Standards and GHTF Guidance
ISO/TC 176/SC 2/N525R2, Introduction and support package: Guidance on
the documentation requirements of ISO 9001:2008
ISO/TR 14969:2004 Medical devices -- Quality management systems -Guidance on the application of ISO 13485: 2003
ISO 14971: 2007 Medical devices -- Application of risk management to
medical devices
ISO IEC 62366: 2007 Medical devices -- Application of usability engineering
to medical devices
ISO IEC 62304: 2006 Medical device software -- Software life cycle processes
GHTF/SG3/N18/2010 Quality Management System - Medical Devices Guidance on corrective action and preventive action and related QMS
processes
GHTF/SG3/N17/2008 Quality Management System - Medical Devices Guidance on the Control of Products and Services Obtained from Suppliers
GHTF/SG3/N15R8/2005 Implementation of Risk Management Principles and
Activities Within a Quality Management System
GHTF/SG3/N99-10 (Edition 2)Quality Management Systems - Process
Validation Guidance

Copyright 2012 ITRI

11

Further Readings:
US FDA Guidance
Application to Device Good Manufacturing Practice Regulation to the
Manufacturer of Sterile Devices, 1982, 1983
Guideline for the Manufacture of In Vitro Diagnostic Products, 1994
Bacteria Edotoxins/Pyrogens, 1995
Guide to Inspections of Foreign Medical device Manufacturers, 1995
21 CFR 801.415 Maximum acceptable level of ozone
Guide to Inspections Validation of Cleaning Processes
Electromagnetic Compatibility Aspects of Medical Device Quality Systems
Medical Device Quality Systems Manual: A Small Entity Compliance Guide,
1996
Do It by Design, 1996
Design Control Guidance for Medical Device Manufacturers, 1997
Medical Device Use-Safety: Incorporating Human Factors Engineering into Risk
Management, 2000
Applying Human Factors and Usability Engineering to Optimize Medical
Device Design, 2011
Residual Ethylene Oxide in Medical Devices and Device Material

Copyright 2012 ITRI

12

ISO/TR 14969: 2004

ISO/TR 14969: 2004 Medical devices Quality management

systems Guidance on the application of ISO 13485:2003

ANSI/AAMI/ISO TIR14969:2004 Medical devicesQuality

management systems Guidance on the application of ISO
13485:2003

YYT0287-2003

CEN ISO/TR 14969:2005

Copyright 2012 ITRI

13

Key Points
4 QMS

4.2.1.1Docuementation
4.2.1.4 MD
Documentation

7. Product
realization

4.2.3.4 Electronic
document
4.2.3.5Rrecord
retaining period
4.2.4. Record control

5.Management
responsibility

6. Resource
management

Copyright 2012 ITRI

5.4.1 Quality objectives

5.4.2 QMS planning

7.1.1.5 Product
requirements
7.1.2 risk management
7.1.3expiration date
7.3 Design and
development

8. Measurement,
analysis, and
improvement

7.4.1 Purchasing process

8.1.2, 8.1.3 Statistical

methods

7.5.1 Control of
production and service
provision

8.2.4 Monitoring and

measurement of
product

7.5.2 Validation of
processes for
production and service
provision

6.4 Work environment

8.5 Improvement

7.6 Control of
monitoring and
measuring devices

14

No Specific Guidance Given in

ISO TR 14969: 2004
3 Terms and definition
4.2.2 Quality manual
5.2 Customer focus
6.2.1 (Human resources) General
7.2.2 Review of requirements related to the product
8.2.3 (Monitoring and measurement of processes)
Monitoring and measurement of processes
8.2.4.2 (Monitoring and measurement of product) Particular
requirements for active implantable ad implantable devices

Copyright 2012 ITRI

15

Design and Development Process

User Needs

Design Review

Design Input

DHF/Technical
Documentation
Premarket
Submission (ex.
STED)

Design Process

Design Verification

Design Output

Medical Device

Design Validation

21 CFR 820.30 Quality System Regulation

ISO 13485: 2003 7.3

Copyright 2012 ITRI

16

Integrated Design Process

DESIGN CONTROL SYSTEM OUTLINE
CHANGE INTEGRATED INTO DESIGN CONTROL

ISO 14971: 2007

Medical Devices
Application of risk
management to
medical devices

GENERAL
820.30 (a)
"EXTERNAL"
REQUEST

PLANNING (b)

INTEGRATED CHANGE
CONTROL
PROCEDURE

IEC 62304:2006 Medical

device software Software life cycle
processes

TRANSFER (h)

VERIFICATION (f)
& VALIDATION (g)

TRANSFER (h) FOR

FULL-SCALE
PRODUCTION

Copyright 2012 ITRI

REVIEW (e)

OUTPUT (d)
----------------------------DMR 820.181

CHANGE REQUEST
FORMS
ID OF DOCUMENTS
REVISION LEVELS
TIMELY

INITIAL
PRODUCTION
DATA FOR
MARKETING
SUBMISSIONS

ISO IEC 62366: 2007

Medical devices
Application of usability
engineering to medical
devices

VERIFICATION (f)

INPUT (c)

DHF (j)

integrated_change_ctrl.doc

17

Medical Device Risk Management

Risk
RiskAnalysis
Analysis

Intended
Intendeduse
useand
andidentification
identificationofofcharacteristics
characteristics
related
to
the
safety
of
the
medical
related to the safety of the medicaldevice
device
Identification
of
hazard
Identification of hazard
Estimation
Estimationofofthe
therisk(s)
risk(s)for
foreach
eachhazardous
hazardoussituation
situation

Risk Assessment

Risk
RiskEvaluation
Evaluation

Risk
Risktolerability
tolerabilitydecisions
decisions
Risk
RiskControl
Control
Risk
Riskcontrol
controloption
optionanalysis
analysis
Implementation
of
risk
control
Implementation of risk controlmeasures
measures
Residual
risk
evaluation
Residual risk evaluation
Risk/benefit
Risk/benefitanalysis
analysis
Risk
arising
from
risk
control
Risk arising from risk controlmeasures
measures

Evaluation
Evaluationof
ofoverall
overallresidual
residualrisk
riskacceptability
acceptability

Risk Management

Risk
Riskmanagement
managementreport
report
Production
Productionand
andpost-production
post-productioninformation
information

Copyright 2012 ITRI

18

Medical Device Hazards

Operational Hazards
Function

Use error

Chemical

Electromagnetic
energy

Thermal energy

Medical Device
Mechanical
energy

Biocompatibility

Labeling

Operating
instructions

Warnings

Energy hazards

Biological and chemical

hazards

Biological

Radiation
energy

Information hazards
IEC 14971:2007, Table E.1 Examples of hazards
http://www.nhlbi.nih.gov/
19
Copyright 2012 ITRI

19

Content
GHTF Medical Device Regulatory Model
QMS for SMEs
Revision of ISO 13485

Copyright 2012 ITRI

20

Revision of ISO 13485

In 2009 ISO/TC 210, Working Group 1 considered

the need for revision of ISO 13485:2003

Prompted by the emergence of new national

medical device regulatory activities from countries
in the South American and Asian Pacific regions, in
2011 the Working Group conducted a formal user
survey to determine the need for a revised standard
and to provide insight into the content of such a
revised standard.

Copyright 2012 ITRI

21

Compatibility with Regulations and

Standards

To converge its requirements further with those in the U.S. FDA

21 CFR Part 820, the Japanese MHLW Ministerial Ordinance No.
169: 2004, and the conformity assessment requirements of the
European medical device legislation, while not intending to
compensate for the deficiencies of such national and regional
regulations.

To address developments in regulatory requirements for QMS

in other jurisdictions.

To maintain requirements compatibility with ISO 9001:2008

(QMS) and ISO 9000:2005 (Fundamentals and vocabulary)

Copyright 2012 ITRI

22

Subjects to Be Addressed in the Text of the

Amended Standard

Focus on QMS requirements, not product requirements, and to emphasize that

the QMS requirements in the standard apply throughout the life cycle of the
products

Product lifecycle management (ISO 15288[System life cycle processes] and ISO
12207[Software life cycle processes])

Software validation requirements such as QMS software and medical device

software

The roles and relationship between the organization and other parties in the
supply chain and outsourcing

Risk management covering product lifecycle

Postmarket information gathering and adverse event reporting, complaint

handling, returned product handling, and CAPA (GHTF SG3 N18 )

Design and development requirements linked to essential requirements, V&V

protocols and so on.

Environmental control, process validation (GHTF SG3/N99-10 ed. 2)

Record retaining time

Annex Z of EN 13485

Copyright 2012 ITRI

23

Enhance QMS
1. Enhanced operating systems
1)

2)
3)

Design and reliability engineering specifically, validation of actual

product use, design-for-reliability and manufacturability, and software
robustness.
Robust postproduction monitoring and feedback into design and
manufacturing that goes beyond base compliance requirements.
Supplier management processes, particularly in material and process
change controls.

2. Enhanced management infrastructure

1)
2)
3)

Quality metrics and measurement systems that go beyond regulatory

compliance measures.
Quality organization that integrates cross-functionally throughout the
organization, rather than solely focused on compliance.
Performance management, where those in key roles associated with
quality outcomes, like design engineers, are measured and
incentivized around quality performance.

3. Enhanced mindsets and behaviors

1)

Quality culture can be improved where companies have experienced

severe quality-related issues.

US FDA, Understanding Barriers to Medical Device Quality, Oct 31, 2011

24
Copyright 2012 ITRI

24

Thank you very much

Albert T.W. Li
Tel: +886-3-573-2227
Fax: +886-3-573-4092
E-mail: alberttwli@itri.org.tw
Copyright 2012 ITRI

Science Industrial Park, Hsinchu

25